Usefulness of Myoglobin Containing Cobalt Heme Cofactor in Designing a Myoglobin-Based Artificial Oxygen Carrier

Abstract

The structure and reactivity of cobalt-replaced myoglobin (Mb) were investigated to explore its possible application as an artificial oxygen carrier. Ligand binding analysis with relaxation kinetics revealed that various ligands bind to Co(III) Mb, contrary to the earlier thoughts. The equilibration process, however, was so slow that it proceeded over 90 min. These characteristic profiles of oxidized Co(III) Mb were ascribed to the electronic structure of Co(III) ion which is one electron larger than Fe(III) ion. The oxygen affinity of reduced Co(II) Mb was much smaller than that of Fe(II) Mb indicating that Co(II) Mb has excellent oxygen transport ability. The latter observation, together with the lack of carbon monoxide binding in Co(II) Mb, suggests utility of Co(II) Mb as Mb-based oxygen carriers. The present results on cobalt-substituted Mb are useful in designing myoglobin-based oxygen carriers.

Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

“…Besides engineering Hgb or the surrounding shell, there are other ideas such as simply using the O 2 binding porphyrin structure of Hgb [e.g., embedded in cyclodextranes (HemoCD)] (Kitagishi et al, 2017) or completely using other materials such as cobalt porphyrins (where the central iron ion in the O 2 -binding structure of Hgb is replaced by cobalt) (Neya et al, 2014;Shen et al, 2016). Furthermore, there have been attempts to directly introduce O 2 into particles, thus for the first time permitting for a safe and effective intravenous injection of O 2 gas, which locally increases pO 2 very rapidly (Seekell et al, 2016;Black et al, 2017).…”

Artificial Oxygen Carrier to Regulate Hypoxic Signal Transduction

“…However, recent recognition of the deterioration of stored human red blood cells (RBCs) (2) has aggravated the already keen demand/supply imbalance of donated blood for transfusion, fueling the continuing endeavor to come up with new concepts and technologies to overcome problems (1) or fulfill new requirements proclaimed by the National Institutes of Health (NIH) (3). In this issue, it is encouraging to report new utilities and recently developed AOCs from recycled human RBCs (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), unlimited hemoglobin (Hb) from bovine RBCs (18)(19)(20)(21), and other sources (22)(23)(24). Some of them are close to or are currently under clinical trial (20).…”

Artificial Oxygen Carrier as Therapeutics Rather Than Blood Substitute for Transfusion

“…While mass‐production of human Hb has yet to reach a practical level, the minimal effective dose of liposome‐encapsulated Hb for various applications could be as low as 120–24 mg/kg of Hb to body weight , reversing the access from the user's side to meet the limited supply and low productivity. Synthetic AOCs have approached a level of experimental application following manufacturing renovations . More interesting are the characteristics of these new and innovative AOCs, which have a huge capacity to combine O 2 per single molecule, 156 O 2 molecules , and 3–8 O 2 molecules per single compound , suggesting that even a smaller dose is required to deliver the necessary amount of O 2 .…”